Hellstrom Ingegerd, Raycraft John, Kanan Sandra, Sardesai Niranjan Y, Verch Thorsten, Yang Yi, Hellstrom Karl Erik
Department of Pathology, Harborview Medical Center, University of Washington, 325 9th Avenue, Box 35 99 39, Seattle, WA 98104, USA.
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):1014-20. doi: 10.1158/1055-9965.EPI-05-0334.
The mesothelin family comprises (at least) three variants and includes the precursor for megakaryocyte potentiating factor (MPF). Assaying soluble mesothelin-related protein (SMRP) molecules in serum and other body fluids from patients with certain cancers can provide diagnostically useful information. We have constructed fusion proteins of mesothelin variants 1, 2, and 3, made monoclonal antibodies, and investigated the binding specificity of these and three previously generated monoclonal antibodies to each of the three mesothelin variants. According to flow cytometry, the molecule that is most frequently expressed at the surface of cells from ovarian carcinomas and certain other tumors is mesothelin variant 1. Similarly, SMRP released into ascites from a patient with ovarian carcinoma was shown to have a molecular weight of approximately 40 kDa and, according to sequencing, to be variant 1. A published sandwich ELISA was shown to detect variants 1 and 3 and to be much more sensitive than a newly constructed ELISA, which detects only variant 3, the former being positive in 28 of 41 (68%) sera from patients with ovarian cancer as compared with 6 of 41 sera (15%). A standard curve was constructed to measure SMRP with a limit of detection of 200 pg/mL to facilitate future quantitative studies.
间皮素家族（至少）包含三种变体，其中包括巨核细胞增强因子（MPF）的前体。检测某些癌症患者血清和其他体液中的可溶性间皮素相关蛋白（SMRP）分子可提供诊断有用信息。我们构建了间皮素变体1、2和3的融合蛋白，制备了单克隆抗体，并研究了这些抗体以及之前产生的三种单克隆抗体与三种间皮素变体各自的结合特异性。根据流式细胞术，卵巢癌和某些其他肿瘤细胞表面最常表达的分子是间皮素变体1。同样，从一名卵巢癌患者腹水中释放的SMRP显示分子量约为40 kDa，经测序为变体1。已发表的夹心ELISA检测变体1和3，且比新构建的仅检测变体3的ELISA更灵敏，前者在41份卵巢癌患者血清中的28份（68%）呈阳性，而后者在41份血清中的6份（15%）呈阳性。构建了标准曲线以测量SMRP，检测限为200 pg/mL，以便于未来的定量研究。
